The Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) is an alternative strategy for relapse prevention in patients with Opioid Use (OUD) and other substance use disorders (SUD). Opioid and other forms of drug addiction can be defined as a failure to control drug-seeking behavior, and reflect an exaggerated drive to consume drugs, and/or an inability to engage in outcome-guided behaviors involving non-drug rewards such as food, health, social status and money. In contrast to overlearned drug-related associations, non-drug outcomes are often less well established and need to be inferred or mentally simulated. The orbitofrontal cortex (OFC) plays important role in regulation of addiction through provision of an associative structure (i.e. cognitive map) for these mental simulations. As a result, OFC inactivation or direct injury from cocaine use or other sources, lead to repetitive drug use. On the other hand, even brief optogenetic activation of OFC activity produce sustained changes in OFC-dependent behaviors, including reduced self-administration of drugs in neurobiology studies. Unfortunately, both cocaine and opioid use negatively impair OFC structure/function, thereby fueling recurrence use of this drug through impairment in OFC-based outcome-guided behaviors for non-drug rewards. Relapses in these patients is further compounded by emotion dysregulation since the OFC is a key structure involved in prefrontal ?top- down? regulation of emotional appraisal. Therefore, neurostimulation of OFC to enhance OFC plasticity has solid scientific premise for treatment of opioid addiction, through improvement of outcome-guided behavior and affective regulation. However, the ventral location of the OFC at the base of the skull makes it less accessible for non-invasive stimulation using direct transcutaneous current stimulation or transcranial magnetic stimulation. An alternative strategy to improve long-term opioid abstinence would be to use high fidelity chemosensory and computerized olfactory training approach to stimulate the OFC, repeatedly and intensively, to influence OFC plasticity and enable more consistent recruitment of this region over time, for outcome-guided behaviors involving non-drug outcomes, and for voluntary suppression of negative emotion. The small business, Evon Medics LLC and Howard University (HU) have created a home-based olfactory pulsing prototype called Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) to enable home- based neuromodulation of the OFC for treatment of OUD. Result of our pilot feasibility study in OUD samples suggest that CBOT can minimize withdrawal symptoms, reduce drug cravings, enhance positive affect and reduce rate of positive urine drug tests. We propose a Phase 1 SBIR application to: establish CBOT stimulation parameters needed to maximally improve outcome inference and emotion regulation in OUD (Aim 1); and conduct a pilot test of short-term effectiveness of CBOT treatment in reduction of recurrent positive urine drug tests over 12 weeks in 20 OUD patients defined by recurrent monthly drug relapse in the past year. Project success will be enhanced through strong collaborations between Evon Medics and HU investigators. The investigative team has significant experience in product and business development, OUD research, olfactory neuroscience, and development and evaluation of OUD interventions. Completion of grant activities will lead to an optimized CBOT product that overcome the drawbacks of traditional olfactory therapy and other noninvasive OFC modulation approaches in prevention of substance relapse in OUD populations with high relapse rate